CompLifeSci seminar: Jukka Westermarck

Time

22.3.2019 at 14.00 - 15.00
Prof. Jukka Westermarck, Centre for Biotechnology and Institute of Biomedicine, University of Turku: Phosphoproteome and Functional Landscape of Protein Phosphatase 2A (PP2A) in Cancer Cells

Host: Tero Aittokallio
Coffee at 13:45

The focus of our laboratory is to understand role and regulation of PP2A in human cancers and especially function of PP2A inhibitor proteins as human oncoproteins. To achieve this, we use a combination of advanced cell and molecular biology approaches combined with genetically modified mouse cancer models. We also have special interest on targeted therapies against PP2A inhibitor proteins. Our recent results suggest that a potential biological outcome of aberrant PP2A signaling in cancer is conferring drug resistance (Cancer Research, 2016, Sci.Transl. Med, 2018). Based both on these results, and on wide-spectrum role of PP2A on cellular signaling, we hypothesize that re-activation of PP2A, via targeting of its endogenous inhibitory proteins, could be used as a general strategy for multi-target inhibition of chemoresistance in common human cancer types. In addition, these results may have importance in patient stratification for monotherapies using the identified small molecule compounds.

Selected publications:

Kauko O, O´Connor CM, Kulesskiy E, Sangodkar J, Aakula A, Izadhmehr S, Yetukuri L, Yadav B, Padzik A, Laajala TD, Haapaniemi P, Momeny M, Varila T, Ohlmeyer M, Aittokallio T, Wennerberg K, Narla G*, and Westermarck J*; PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. Science Translational Medicine 10(450), doi: 10.1126/scitranslmed.aaq1093, 2018.

Kaur A, Denisova OV, Qiao X, Jumppanen M, Peuhu E, Ahmed SU, Raheem O, Haapasalo H, Eriksson J, Chalmers AJ, Laakkonen P and Westermarck J; PP2A inhibitor PME-1 drives kinase inhibitor resistance in glioma cells. Cancer Research 76(23): 7001-7011, 2016.

Laine A, Sihto H, Come C, Rosenfeldt MT, Zwolinska A, Niemelä M, Khanna A, Chan EK, Kähäri V-M, Kellokumpu-Lehtinen P-L, Sansom OJ, Evan GI, Junttila MR, Ryan KM, Marine J-C, Joensuu H, and Westermarck J; Senescence sensitivity of breast cancer cells is defined by positive feedback loop between CIP2A and E2F1. Cancer Discovery 3(2): 182-197, 2013.

Puustinen P, Junttila MR, Vanhatupa S, Sablina AA, Hector ME, Teittinen K, Raheem O, Ketola K, Lin S, Kast J, Haapasalo H, Hahn WC, and Westermarck J; PME-1 protects ERK pathway activity from protein phosphatase 2A-mediated inactivation in human malignant glioma. Cancer Research 69: 2870-2877, 2009.

Khanna A, Böckelman C, Hemmes A, Junttila MR, Wiksten J-P, Lundin P, Junnila S, Murphy D, Evan GI, Haglund C, Westermarck J*, and Ristimäki A*; MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. Journal of the National Cancer Institute 101: 793-805, 2009.
Junttila, MR, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, Ala-aho R, Nielsen C, Ivaska J, Taya Y, Lu SL, Li S, Chan EKL, Wang X-J, Grenman R, Kast J, Kallunki T, Sears R, Kähäri V-M, and Westermarck J; CIP2A inhibits PP2A in human malignancies. Cell 130: 51–62, 2007

Additional information

Nurmi, Miina